CB1 vs CB2 Receptors for the Treatment of Pain

Chronic pain is one of the greatest costs to the individual and to society. Many of the myriad conditions that cause chronic pain have a common identity: they are caused or cause chronic inflammation. This stresses the body and raises the risks of many kinds of disease. The endocannabinoid system is vitally involved with the inflammatory response and with pain, making it a crucial target for the effective treatment of chronic pain.

CB1 and CB2 receptors are the two main receptors in the endocannabinoid system. They are mediated by cannabinoids, which are naturally occurring in the cannabis plant and in the brain. Synthetic cannabinoids have been developed. Both neuropathic and inflammatory origins of pain can be targeted with cannabinoids through activation of the central nervous system’s ECN.

Topical application of THC (which is psychoactive through its interaction with the ECN) is an effective anti-inflammatory, however it is not as effective as orally administered THC. The psychoactivity and CNS side effects make it intolerable or inappropriate for many people. An orally administered drug that did the same job as THC but did not produce psychoactivity was seen as a very useful thing.

This paper examined indoles and indenes, both of which are agonists for CB1 receptors. It is hoped that these chemicals, which do not pass the blood brain barrier, can be targeted at peripheral inflammatory and neuropathic pain without the CNS side effects like psychoactivity seen with some cannabinoids.

The results were promising, with PRCB compounds developed in the study showing “high peripheral selectivity CB1R agonists to exhibit, after systemic or oral administration, potent, and repeated suppression of neuropathy symptoms with a lack of side effects “.

Cannabinoids for the Treatment of Pain

During the assays, the experimental team selectively narrowed down the potential CB1 receptor agonists with a series of simulations and experiments. Eventually, several compounds were developed that showed a high affinity to CB1 receptors. These were chosen because they did not pass through the blood brain barrier, so were ideal for peripheral inflammation and neuropathy. High doses can be administered without CNS side effects unlike THC or other blood-brain barrier permeable cannabinoids and synthetic cannabinoids.

In vivo testing was carried out to gauge the potential side effects of the cannabinoids developed in this study. They were found to be minimal. Further testing will be required before a full safety profile can be developed but it is promising. Furthermore, the cannabinoids showed high potency, meaning relatively small doses will be needed if the drug goes to phase 3 trials and to market.

The blood brain barrier impermeability is particularly useful because the central nervous system does not get affected. This allows for relatively high doses of a drug that affects nerves to be administered without messing with the delicate balances in a healthy brain. The majority of inflammatory and neuropathic pain conditions occur outside of the central nervous system, so many different therapeutic applications can be imagined.

These drugs are potentially very useful. Cannabis has been known to be an effective anti-inflammatory for a long time but its continuing illegality and the side effects put many people off using them. The development of cannabinoids that can do the same job without the legal difficulties and the side effects is exciting and could help a lot of people.

CB1 receptors are the targets of THC, the psychoactive part of the cannabis plant. These synthetic cannabinoids bind to the same receptor as THC but cannot penetrate the blood brain barrier, leaving the central nervous system alone and therefore producing no psychoactive effects. They appear tolerable, safe and effective. More study is required before they can be properly assessed as drugs, however.

Registered with the British Psychological Society, breaking the taboo on mental health issues is one of the driving forces in Jonathan's life. His background in biomedicine gives him additional understanding of the factors that work together to influence the human condition.